陕西地区10165例造血干细胞捐献者HLA-A/B/DRB1座位罕见等位基因确认与分析

Identification and Analysis of the Rare HLA-A/B/DRB1 Allele Genes of 10165 Bone Marrow Registry Donors in Shaanxi Region

本研究分析陕西地区2009-2012年度10165例造血干细胞捐献者HLA-A/B/DRB1分型中罕见等位基因的检出状况。应用PCR-SBT方法对10165陕西地区造血干细胞捐献者的HLA-A/B/DRB1进行分型。结果发现,在48例捐献者中确认罕见等位基因40种,其中在15个捐献者中确认的10种等位基因虽不包含在中华骨髓库的常见及确认等位基因表(common alleles and well documented alleles,CWD)中,但已包含在美国免疫遗传协会的常见及确认的等位基因表中,分别是:A*02:04、B*07:10、B*27:09、B*35:11、B*44:29、DRB1*03:04、DRB1*08:18、DRB1*13:05、DRB1*13:14、DRB1*14:11,检出2例以上的罕见等位基因包括A*68:24、B*35:11、B*44:29、DRB1*03:04、DRB1*08:18、DRB1*13:05。本实验室从2005-2012年发现并被世界卫生组织人类白细胞抗原因子命名委员会命名的共21例新的HLA等位基因中,有些在多个实验室的多个个体被确认,现已有HLA-A*02:90、HLA-B*48:14、HLA-DRB1*01:14被列入中华骨髓库的确认及常见等位基因表。结论:在实际工作中,对于发现的新等位基因要及时上报,对确认的罕见等位基因要记录统计,保证中华骨髓库HLA基因人群分布不断累积和多态性完整,给修正中国CWD表提供依据。在参照常见及确认等位基因表进行实验分析时,对于模棱两可样本含有已确认过的罕见等位基因时要慎重取舍,以避免错检或漏检发生,保证患者尤其是携带罕见等位基因的患者最大可能的找到匹配的供者。

This study was purposed to analyze the detected status of rare alleles from HLA-A/B/DRB1 typing of 10165 unrelated hematopoietic stem cell donors in Shaanxi region during 2009 -2012. The rare allele distributions of HLA-A/B/DRB1 gene typing of 10165 unrelated-donors from Shaanxi sub-registry of Chinese National Marrow Donor Project （CMDP） were detected and analyzed by PCR-SBT. The results showed that there were 40 rare alleles from 48 donors identified by PCR-SBT in 10165 unrelated-donors of Shaanxi sub-registry. Among them, 10 rare alleles of A ＊ 02：04, B＊07：10, B＊27：09, B＊35：11, B＊44：29, DRB1 ＊03：04, DRB1＊08：18, DRB1 ＊ 13：05, DRB1 ＊ 13：14 and DRB1 ＊ 14：11 from 15 donors were not included in the common alleles and well documented alleles（CWD） of China, but were included in the CWD of American Society for Histocompatibility and Immunogenetics （ASHI）. The alleles of A＊68：24, B ＊ 35：11, B ＊44：29, DRB1 ＊03：04, DRB1 ＊08：18 and DRB1 ＊ 13：05 were confirmed in more than two samples. There were totally 21 novel HLA alleles identified by our laboratory and officially assigned by the WHO Nomenclature Committee from 2005 to 2012, and some of them were also detected from multiple donors in other HLA typing laboratories of China. Now the novel alleles of HLA-A＊ 02：90, HLA-B ＊ 48 ： 14 and HLA-DRB1 ＊ 01：14 were added into the Chinese CWD list. It is concluded that to ensure the polymorphism integrity and accurate population distribution of HLA genes and its constant accumulations on CMDP, it is necessary to recognize and submit timely the potential novel alleles in our practical work, as well as to record and statistics the identified rare alleles, which can provide the basis for the modification of Chinese CWD. When CWD list is refered, it should be careful for ambiguous results containing the identified rare alleles in order to avoid the occurrence of false or undiscovered detection,and ensure that the patients carrying rare alleles could find a matching donor with the maximum opportunity.